Ultrafast and long-range coordination of wound responses is essential for whole-body regeneration.
Ultrafast and long-range coordination of wound responses is essential for whole-body regeneration.
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伤口反应的超快和远距离协调对于全身再生至关重要。
DOI：
10.1101/2023.03.15.532844
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发表时间：
2023
期刊：
影响因子：
--
通讯作者：
Wang,Bo
中科院分区：
文献类型：
--
作者：
Fan,Yuhang;Chai,Chew;Li,Pengyang;Zou,Xinzhi;FerrellJr,JamesE;Wang,Bo
伤害会引发系统性的、全球性的反应，其功能仍然难以捉摸。此外，在整个生物体范围内，通过长距离快速同步伤口反应的机制大多尚不清楚。利用具有极强再生能力的浮游生物，我们报道了损伤诱导ERK活性以意想不到的速度(~1 mm/h)以波状方式移动，比在其他多细胞组织中测得的速度快10-100倍。这种超快的信号传播需要纵向的体壁肌肉，拉长的细胞形成密集的平行轨道，贯穿整个生物体。结合实验和计算模型，我们发现，肌肉的形态特征使它们能够最大限度地减少缓慢的细胞间信号步骤，并充当双向高速公路，传播创伤信号，并在其他类型的细胞中指示反应。抑制Erk的增殖可以防止伤口远处的细胞做出反应，并阻止再生，而再生可以通过在第一次损伤后的狭窄时间窗口内对远端组织进行第二次损伤来挽救。这些结果表明，远离伤口的未损伤组织的快速反应对于再生是必不可少的。我们的发现为大而复杂的组织中的远程信号传播提供了一种机制，以协调不同细胞类型的细胞反应，并强调了在全身再生过程中空间分离的组织之间的反馈功能。
Injury induces systemic, global responses whose functions remain elusive. In addition, mechanisms that rapidly synchronize wound responses through long distances across the organismal scale are mostly unknown. Using planarians, which have extreme regenerative ability, we report that injury induces Erk activity to travel in a wave-like manner at an unexpected speed (~1 mm/h), 10–100 times faster than those measured in other multicellular tissues. This ultrafast signal propagation requires longitudinal body-wall muscles, elongated cells forming dense parallel tracks running the length of the organism. Combining experiments and computational models, we show that the morphological properties of muscles allow them to minimize the number of slow intercellular signaling steps and act as bidirectional superhighways for propagating wound signals and instructing responses in other cell types. Inhibiting Erk propagation prevents cells distant to the wound from responding and blocks regeneration, which can be rescued by a second injury to distal tissues within a narrow time window after the first injury. These results suggest that rapid responses in uninjured tissues far from wounds are essential for regeneration. Our findings provide a mechanism for long-range signal propagation in large and complex tissues to coordinate cellular responses across diverse cell types, and highlights the function of feedback between spatially separated tissues during whole-body regeneration.